The Rap GTPases mediate CXCL13- and sphingosine1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes

Authors

  • Caylib A. Durand,

    1. Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
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  • Jens Westendorf,

    1. Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
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  • Kathy W. K. Tse,

    1. Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
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  • Michael R. Gold

    Corresponding author
    1. Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada, Fax: +1-604-8226041
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Abstract

The localization of B cells to lymphoid organs where they can become activated and differentiate into antibody-secreting plasma cells is controlled by multiple chemoattractants that promote cell migration and integrin-mediated adhesion. CXCL13 and sphingosine 1-phosphate (S1P) are two important chemoattractants that control the trafficking of B cells. CXCL13 directs B lymphocytes to lymphoid follicles where they receive survival signals and, if activated, undergo a germinal center response. In contrast, S1P allows B cells and plasma cells to exit lymphoid organs and re-enter the circulation. The Rap1 GTPase is a key regulator of cell adhesion and cell migration in a number of systems. We now show that Rap activation is required for CXCL13 and S1P to induce B cell migration as well as adhesion to ICAM-1 and VCAM-1. We also show that Pyk2, a tyrosine kinase involved in cytoskeleton rearrangements and B cell migration, is a downstream target of both CXCL13 and S1P signaling and that Rap activation is important for CXCL13 and S1P to stimulate tyrosine phosphorylation of Pyk2, a modification that increases Pyk2 kinase activity. This suggests that the ability of CXCL13 and S1P to direct the trafficking and localization of B cells in vivo may be dependent on Rap activation.

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